David R. Langdon

OBJECTIVE: Heterozygous activating mutations of glucokinase have been reported to cause hypoglycemia attributable to hyperinsulinism in a limited number of families. We report three children with de novo glucokinase hyperinsulinism mutations who displayed a spectrum of clinical phenotypes corresponding to marked differences in enzyme kinetics. RESEARCH DESIGN AND METHODS: Mutations were directly sequenced, and mutants were expressed as glutathionyl S-transferase-glucokinase fusion proteins. Kinetic analysis of the enzymes included determinations of stability, activity index, the response to glucokinase activator drug, and the effect of glucokinase regulatory protein. RESULTS: Child 1 had an ins454A mutation, child 2 a W99L mutation, and child 3 an M197I mutation. Diazoxide treatment was effective in child 3 but ineffective in child 1 and only partially effective in child 2. Expression of the mutant glucokinase ins454A, W99L, and M197I enzymes revealed a continuum of high relative activity indexes in the three children (26, 8.9, and 3.1, respectively; wild type = 1.0). Allosteric responses to inhibition by glucokinase regulatory protein and activation by the drug RO0281675 were impaired by the ins454A but unaffected by the M197I mutation. Estimated thresholds for glucose-stimulated insulin release were more severely reduced by the ins454A than the M197I mutation and intermediate in the W99L mutation (1.1, 3.5, and 2.2 mmol/l, respectively; wild type = 5.0 mmol/l). CONCLUSIONS: These results confirm the potency of glucokinase as the pancreatic beta-cell glucose sensor, and they demonstrate that responsiveness to diazoxide varies with genotype in glucokinase hyperinsulinism resulting in hypoglycemia, which can be more difficult to control than previously believed.

OBJECTIVE: To examine vitamin D levels in children with (1) suspected abusive and accidental fractures, (2) single and multiple fractures, and (3) fracture types highly associated with inflicted trauma. DESIGN AND METHODS: A study of children younger than 2 years of age with fractures admitted to a large children's hospital was performed. Bivariate analysis and test for trend were performed to test for the association of vitamin D status and biochemical markers of bone health with the primary outcomes of fracture etiology, number, and type. RESULTS: Of 118 subjects in the study, 8% had deficient vitamin D levels (<20 ng/mL; <50 nmol/L), 31% were insufficient (≥20 < 30 ng/mL; ≥50 < 78 nmol/L), and 61% were sufficient (≥30 ng/mL; ≥78 nmol/L). Lower vitamin D levels were associated with higher incidences of hypocalcemia (P = .002) and elevated alkaline phosphatase (P = .05) but not hypophosphatemia (P = .30). The majority of children sustained accidental fractures (60%); 31% were nonaccidental and 9% were indeterminate. There was no association between vitamin D levels and any of the following outcomes: child abuse diagnosis (P = .32), multiple fractures (P = .24), rib fractures (P = .16), or metaphyseal fractures (P = .49). CONCLUSIONS: Vitamin D insufficiency was common in young children with fractures but was not more common than in previously studied healthy children. Vitamin D insufficiency was not associated with multiple fractures or diagnosis of child abuse. Nonaccidental trauma remains the most common cause of multiple fractures in young children.

PURPOSE: To assess the effectiveness of and outcomes with a twin catheter system. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records, hemodialysis records, and clinical information system data from 132 consecutive patients who were referred for placement of a tunneled catheter for hemodialysis access. A commercially available twin catheter system was placed in all patients. Outcomes evaluated included infection rate, complication rate, and catheter malfunction and failure rates. Performance parameters evaluated included blood flow rates, urea reduction percentages, and recirculation percentages. RESULTS: One hundred eighty-four twin catheter systems were placed in 132 patients from January 11, 1996, to October 23, 1997. The initial technical success rate was 100%. There were four immediate procedural complications: Air emboli occurred in two patients, and prolonged bleeding necessitating intervention occurred in two. The total number of days a catheter was in place was 13,200 (mean, 74.6 days). Thirty-one infections occurred in 20 patients (total infection rate, 0.23 episodes per 100 catheter days). Sixty-five catheters malfunctioned during the study period, 19 of which necessitated removal, for a rate of 0.14 episodes per 100 catheter days. The average blood flow rate was 281.4 mL/min (range, 117.1-405.6 mL/min; median, 295.2 mL/min). Mean and median urea reductions were both 61%. Mean and median recirculation was 6.1% and 3.5%, respectively (range, 0%-31%). CONCLUSION: Percutaneous placement of the tunneled twin catheter system can be performed with excellent technical success and safety and acceptable catheter performance and outcomes for effective intermediate- to long-term hemodialysis.

PURPOSE: To compare the outcomes and costs of percutaneous transluminal renal angioplasty (PTRA), percutaneous transluminal stent placement (PTSP) of renal arteries, and renal arterial bypass grafting (RABG) in treatment of renovascular hypertension. MATERIALS AND METHODS: Medical records and angiograms of 130 patients who underwent PTRA, PTSP, or RABG were retrospectively studied to determine success and complication rates, angiographic stenoses, blood pressures, antihypertensive medications, and serum creatinine levels. Actual costs were analyzed in detail. RESULTS: Technical success rates for PTRA, PTSP, and RABG were 91%, 98%, and 92%, respectively. Complication rates were 13%, 16%, and 38%, respectively. The mean arterial pressure was initially lowered by 29.2 mm Hg, 30.3 mm Hg, and 27.3 mm Hg, respectively, and maintained at 21.0 mm Hg, 19.8 mm Hg, and 20.2 mm Hg below baseline at 12 months. The number of antihypertensive medications was initially reduced on average by 0.63, 0.72, and 0.58, respectively, but returned to baseline in all patients by 12 months. The serum creatinine level did not change substantially with any treatment. Initial treatment costs were $1,402, $2,573, and $15,393, respectively. CONCLUSION: PTRA, PTSP, and RABG were equally efficacious for control of renovascular hypertension. The initial treatment cost for bypass grafting was substantially higher than that for PTRA and PTSP of renal arteries.